The regulation of intracellular Calcium is essential for Cardiac Cell Function. One of the important subcellular organelles responsible for a large part of calcium intracellular regulation is the sarcoplasmic reticulum. Calcium uptake into cardiac sarcoplasmic reticulum is modulated by the beta adrenergic amines cascade reaction which is mediated by the 22K dalton protein phospholamban and possibly a 6K dalton protein. Calmodulin is also involved in the regulation of phospholamban phosphorylation and thus affecting Ca2+ uptake. This proposal is directed towards the elucidation of molecular mechanisms involved in the modulation of Ca2+ uptake due to the phosphorylation of phospholamban by c-AMP dependent protein kinase and Ca2+ calmodulin systems. Our laboratory has purified phospholamban and ATPase and thus can carry out reconstitution experiments to understand the role of phospholamban and 6K dalton protein in Ca2+ uptake.